1. Field of the Invention
This invention relates to semisynthetic macrolides, and, more particularly, to 4"-deoxy-4"-acylamido derivatives of oleandomycin, its 11- and 2'-monoalkanoyl and 11,2'-dialkanoyl esters, erythromycin A, its 11- and 2'-monoalkanoyl and 11,2'-dialkanoyl esters, and 6,9-hemiketal derivatives, erythromycin B and its 2'-monoalkanoyl ester, erythromycin A carbonate and its 2'-monoalkanoyl esters and 6,9-hemiketal derivatives, and erythromycylamine, to methods for their preparation and to their use as antibacterial agents.
2. Description of the Prior Art
Oleandomycin and erythromycin are macrolide antibiotics produced by fermentation and described in U.S. Pat. Nos. 2,757,123 and 2,653,899, respectively. Numerous derivatives of oleandomycin and of erythromycins A and B have been prepared in efforts to modify their biological and/or pharmacodynamic properties.
Derivatization of oleandomycin has focused primarily upon the formation of esters at one or more of the hydroxy groups located at the 2'-, 4"- and 11-positions. Mono-, di- and triacyl esters wherein the acyl moiety is derived from a lower aliphatic hydrocarbon monocarboxylic acid having from 2 to 6 carbon atoms are described in U.S. Pat. No. 3,022,219. Aminohydrin derivatives of oleandomycin are reported by Kastons, et al., Khim. Geterosikl. Soedin (2) 168-71 (1974); C.A. 80, 145986n (1974). The compounds, for which no utility is reported, are prepared by treating oleandomycin with a dialkylamine or a heterocyclic amine in a sealed tube for 20 hours at 30.degree. C. The epoxide moiety at the 8-position is the site of reaction.
Various monoesters and cyclic anhydrides of erythromycin are reported in Antibiotics Annual, 1953-1954, Proc. Symposium Antibiotics (Washington, D.C.), pages 500-513 and 514-521, respectively. U.S. Pat. No. 3,417,077 describes the cyclic carbonate ester of erythromycin A, the reaction product of erythromycin A and ethylene carbonate, as an active antibacterial agent. U.S. Pat. No. 3,884,903 discloses 4"-deoxy-4"-oxo-erythromycin A and B derivatives as useful antibiotics.
The 9-amino derivative of erythromycin A, known as erythromycylamine, has been extensively investigated and derivatized. Sulfonamide derivatives of erythromycylamine are described in U.S. Pat. No. 3,983,103 as antibacterial agents. N-alkyl derivatives of erythromycylamine are reported by Ryden, et al., J. Med. Chem., 16, 1059 (1973) to have in vitro and in vivo antibacterial activity.